In the project we are using our three-dimensional structure of the thyroid hormone receptor to design mutations which enable us to test selective functions of the receptor. The thyroid hormone receptor is now known to be a multifunctional protein, although the mechanisms of its various actions are not defined. To date, mutations which are found in patients or by random mutagenesis in yeast models generally lead to mutants with global effects on the protein structure. These are difficult to interpret mechanistically. By using the structure as a guide, we are now able to create mutations which easily lead to loss of individual functions, with no effect on other functions. The graphics facilities at the Computer Graphics Laboratory are of critical importance to design and interpret these mutations.